Progression of calcific aortic valve sclerosis in WHHLMI rabbits

• Published in: Atherosclerosis 2018-06, Vol.273, p.8-14
• Main Authors: Hara, Tetsuya, Tsukada, Norie, Okano, Mitsumasa, Ishida, Tatsuro, Hirata, Ken-ichi, Shiomi, Masashi
• Format: Article
• Language: English
• Subjects: Aortic valve stenosis; LDL-Cholesterol; WHHLMI rabbits
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2018.03.044

Aortic valve stenosis (AS) is the most common valvular heart disease and can be life-threatening. The pathogenesis of aortic valve calcification remains largely unknown, primarily due to the lack of an adequate animal model. The high-cholesterol diet-induced AS model in rabbits is one of the established models, but it has the significant limitation of liver dysfunction leading to low survival rates. We hypothesized that a myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbit, an animal model of familial hypercholesterolemia and atherosclerosis, is a useful animal model of AS. WHHLMI rabbits, aged 20 months and 30 months (n = 19), and control Japanese White rabbits (n = 4), aged 30 months, were used and evaluated by echocardiography under anesthesia. Pathological evaluation and quantitative analyses by polymerase chain reaction (PCR) were also performed. The lipid profile was similar between 20 months and 30 months. Two rabbits died due to spontaneous myocardial infarction during the study. Thirty-month-old WHHLMI rabbits exhibited significantly smaller aortic valve area (0.22 ± 0.006 cm2vs. 0.12 ± 0.01 cm2, p